<p>Seizure is characterized by stereotyped, repetitive activity often with abnormal eye movements. Neonatal seizure is one of the strongest risk factors for neurologic morbidity. Incidence is 4.4 per 1000 live births.</p></sec><sec id="sec002"><title>Four main types

Tonic: extension of arms & legs, stiffening of body

May result from lack of cerebral inhibition (brain stem release phenomenon) and not represent cortical electrical discharges

Seen more often in premature infants (with intraventricular haemorrhage) and common with structural damage rather than metabolic disturbance

Clonic: repeated irregular jerking movements rarely sustained for long

May be focal/multifocal

Multifocal clonic seizures are an indicator of severe generalized cerebral disturbance such as hypoxic encephalopaphy (HIE).

Subtle: sucking, rowing, pedaling, swimming movements

Hard to distinguish from normal activity or sleep movements.

Myoclonic: single or multiple rapid flexion or extension movements of extremities

Suggestive of severe diffuse brain damage

Differential Diagnosis of Epileptic Seizures

Jitteriness: Usually stimulus provoked, ablated with change in posture or restraint and no abnormal eye movements.

Recurrent apnea: May be manifestation of a seizure, especially if associated with tonic posturing

Opisthotonos: Prolonged arching of back without abnormal eye movements, usually due to meningeal irritation.

Etiology of Neonatal Seizures

CNS

Hypoxic-ischemic encephalopathy

Sepsis with meningitis or other intracranial infections

Vascular accidents: Intraventricular hemorrhage/subarachnoid hemorrhage/cerebral venous thrombosis/infarcts

Birth trauma (laceration of tentorium or falx/subdural hematoma)

Metabolic

Hypocalcemia/hypoglycemia/hyponatremia-hypernatremia

Inborn errors of metabolism.

Drug withdrawal: (maternal/neonatal) morphine, barbiturates, heroin, methadone

Structural malformations: cerebral dysgenesis, neuro cutaneous syndromes, peroxisomal disorders.

Miscellaneous: Bilirubin encephalopathy, glycine encephalopathy.

EvaluationHistory

Birth history:

Gestational age

Maternal diabetes, IUGR, Maternal drug use

Traumatic delivery, prolonged labour

History suggestive of perinatal asphyxia

Family history of seizures:

With similar presentation and transient nature in siblings or parent suggests benign familial neonatal convulsions (ask grandparents as parents often do not know)

Neurocutaneous disorders may also be inherited

Age at onset

Right from birth, few hours later, or after days

Seizures within first 24–48 hrs

Consider Hypoxic ischemic encephalopathy (HIE) as first possibility particularly in a term infant with a history of perinatal depression

Consider early onset sepsis

Consider drug withdrawal

Evaluate for intra-ventricular hemorrhage (IVH) in a preterm neonate

Evaluate for transient metabolic abnormalities such as hypoglycemia/hypocalcemia (either primary or secondary to underlying problems e.g. IDM/Polycythemia/poor feeding etc)

Investigations

Blood glucose, Serum calcium, Blood gases

Sepsis evaluation: Blood culture/Sepsis screen, Csf exam andculture

Cranial ultrasonography

Seizures after first few days of life in a sick neonate

Evaluate for sepsis, transient metabolic derangements, IVH in a Preterm neonate

Consider possibility of inborn errors of metabolism

Investigations

Glucose, Calcium, Sodium, Urea, Creatinine, Bilirubin, Ammonia, ABG

Sepsis evaluation as above

Neuroimaging

Serum amino acids, Urine for amino acids, urine organic acids, Tandem Mass Spectroscopy(TMS)

Seizures after first few days of life in a well looking neonate

Benign familial seizures (usually history is suggestive)

Non-familial seizures (fifth day seizure)

Pyridoxine dependency seizures

Investigations

To rule out other causes as mentioned above

Treatment

Confirm seizure

Resuscitate the newborn: Perform ABC, Maintain airway, Ensure breathing, Maintain circulation

Obtain blood sugar by dextrostix/glucometer. If low treat hypoglycemia with IV dextrose 200 mg/kg bolus (which in most instances shall be able to correct hypoglycaemia and abort seizures due to hypoglycaemia, however you may need to use higher doses up to 500 mg/kg as bolus).

If seizures stop after correction of hypoglycaemia, maintain continuous infusion of glucose at a rate of 6–8 mg/kg/min and treat underlying cause for hypoglycaemia.

If seizures persist, obtain sample for calcium, magnesium and electrolytes measurment along with a sepsis screen and start anticonvulsants.

Anti-epileptic drugs (AED)

Phenobarbital is first-line medication to treat seizures. Load with 20 mg/kg IV over 20 minutes. If seizures persist administer additional dose(s) of 5 mg/kg till seizures are controlled. A maximum of 40 mg/kg cumulative dose can be given.

If seizures persist, give phenytoin in a loading dose of 20 mg/kg diluted in normal saline (never in dextrose solution) over 20 minutes and repeat if required to maximum of 40 mg/kg total dose.

If seizures persist, consider use of pyridoxine in a dose of 50–500 mg preferably with EEG, which usually abolishes seizure activity immediately if the cause is pyridoxine defeciency or dependency.

If still seizures persist, consider use of other anticonvulsants like benzodiazepines (midazolam, lorazepam, clonazepam), valproate and rule out causes of refractory seizures like congenital malformations of brain or inborn errors of metabolism. After control of seizures, start maintenance dose of phenobarbitone @ 3–5 mg/kg/day (maintain levels to 10–40 μg/ml) phenytoin @ 5–7 mg/kg/day (maintain levels to 2040 μg/ml).

Algorithmic approach to neonate with suspected seizure

Duration of AED therapy

It depends upon underlying aetiology and neurological status. AED therapy can be discontinued after two seizurefree weeks in most patient groups.

Seizures in Hypoxic ischemic encephalopathy (HIE) usually burn out by 72 hrs and do not require AED for a long period.

Newborns with congenital or destructive brain lesions on neuroimaging, those with Inborn error of metabolism or those with persistently abnormal results on neurological examination at discharge may require a slower tapering of medication over several weeks or months.

AED administration need not be maintained past 3 months of age, even in the child at risk, such infants should be thorougly evaluated on follow up.

Role of EEG

EEG might be helpful in confirming seizure activity in doubtful cases. It helps in deciding need for AEDs. It can also tell about control of seizure activity with AED and background abnormality, which helps in prognostication.

Approach to Neonatal Seizures